Development of novel antibiotics is of utmost urgency, considering the increase in multi-drug resistant strains[unreadable] in diseases like tuberculosis, malaria, AIDS, and the emergence of hitherto unknown diseases such as[unreadable] SARS. Infectious diseases, especially those that involve drug resistant pathogens, have been exacerbated[unreadable] by socioeconomic factors, resulting in widespread health disparities among minority populations. Our long[unreadable] term objective is to discover and develop novel antibiotics to combat infectious diseases (in particular those[unreadable] caused by drug resistant pathogens), contributing to the effort of elimination of health disparities. As a[unreadable] subproject of an application for Research Infrastructure in Minority Institutions (RIMI) Program support, we[unreadable] propose to advance antibiotic drug discovery through complementary and integrated novel approaches from[unreadable] the host defense, the microbial genomic, and the fundamental molecular recognition perspectives. In[unreadable] particular, we will assess the potential of natural host defense lipids as antimicrobial therapeutics, building on[unreadable] the foundation of our recent experimental data in support of lipids' novel in vivo defensive roles. On another[unreadable] front, we will leverage the increased research capacity to identify additional novel chemical structures with[unreadable] antimicrobial activities through high throughput screening of diverse compound libraries. Anticipating a[unreadable] steady provision of potent antibacterial compounds, we will attempt to develop a novel and more efficient[unreadable] method of identifying the cellular targets for these potent inhibitors (including lipid-based inhibitors) through[unreadable] modulated expression of essential target proteins. Furthermore, we will probe and evaluate the molecular[unreadable] cation-pi interaction as a potential novel mechanism of ligand-protein recognition and binding, the result of[unreadable] which would provide new insight and strategies for rational drug design for those newly discovered and[unreadable] prioritized antimicrobial target-inhibitor pairs. With guidance from internal and external mentors and access[unreadable] to high throughput screening and chemical/molecular analysis instrumentation through RIMI funding[unreadable] mechanism, the investigators will be able establish a novel and integrated drug discovery platform that will[unreadable] contribute to the fight against drug resistant pathogens and the effort to eliminate health disparities among[unreadable] minority populations.